Over the course of a few decades, the prevalence of overweight US adults has risen to over 65 percent of the population. The World Health Organization now considers obesity one of the top five health concerns in developed nations. Obesity places individuals at elevated risk for such adverse health outcomes as diabetes, hypertension, heart disease, stroke, and certain types of cancer. In the United States, obesity-related costs are estimated to account for 5-7 percent of annual medical expenditures, or over $75 billion a year. The causes for the recent epidemic are complex and include genetic predisposition, increasingly sedentary lifestyles, and the proliferation of highly palatable and calorically dense foods. Such diets, commonly high in fat and sugar, promote intake beyond that needed to maintain normal body weight. This tendency to overeat served us well when famine occurred regularly but now contributes to the obesity epidemic. The only current centrally active drug approved for weight maintenance (sibutramine) is thought to inhibit feeding by promoting brain serotonergic function. Recent work suggests that serotonin receptors in hypothalamic regions (which modulate food intake based on energy need), and in the hindbrain mediate at least some of these effects. However, promotion of feeding based on the palatable properties of food is thought to be regulated by other brain regions: specifically, the neural reward circuitry that also mediates the addictive properties of drugs of abuse. Using established behavioral pharmacological approaches, this project will test the hypothesis that serotonin receptors in the rat nucleus accumbens and ventral tegmentum regulate food consumption and food-seeking behaviors. Determining the functions of serotonin receptors in this brain motivational circuitry will provide novel information about serotonin's modulation of motivated behavior that is essential for developing and refining pharmacological treatments for weight control. The project will also train and mentor promising undergraduate and Master's students in biomedical research. PUBLIC HEALTH RELEVANCE: The proposed research will achieve all 3 goals of the NIH AREA program: First, it will determine examine the role of individual serotonin receptors within brain reward circuitry in regulating the seeking and consumption of food, which is relevant and essential to developing effective treatment strategies to combat the severe public-health problem of obesity. Second, it will enhance the research environment at Wake Forest University. Finally, it will contribute to the research training of BA and MA students destined for research careers in the behavioral and biomedical sciences.